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Lower HDL cholesterol to combat infertility: study Health

By reducing high levels of cholesterol with a bacterial protein, researchers at Houston Methodist demonstrated another link between high cholesterol and female infertility in sterile rats. One in five American women of reproductive age are unable to conceive after a year of trying, so this is an encouraging development.

Lower HDL cholesterol to cope with infertility: study (Olia Danilevich)
Lower HDL cholesterol to cope with infertility: study (Olia Danilevich)

“We’re dealing with a protein, called serum opacity factor, with unique characteristics,” said Corina Rosales, assistant research professor of molecular biology in medicine with the Houston Methodist Research Institute and lead author of the study. “In our experiments, serum opacity factor reduced cholesterol levels by more than 40 percent in three hours. So, this protein is very potent.”

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The results are published in the American Society for Biochemistry and Molecular Biology’s Journal of Lipid Research.

While the primary function of this protein is to increase bacterial colonization, it also alters the structure of cholesterol-carrying high-density lipoprotein, or HDL, making it easier for the liver to dispose of excess cholesterol that prevents pregnancy. . The researchers also said that serum opacity factor’s dramatic action on HDL could be taken as a potential alternative to statins, which are the current gold standard for lowering cholesterol in people with atherosclerosis.

HDL, known as “good cholesterol,” carries excess cholesterol from various tissues to the liver for breakdown, thereby lowering cholesterol levels. However, if HDL is dysfunctional, lipid metabolism is altered, which, like its counterpart LDL or low-density lipoprotein, can be harmful. Often called “bad cholesterol,” LDL carries cholesterol from the liver to other tissues, with high levels causing accumulation and disease.

“Both HDL and LDL contain a mixture of free and esterified cholesterol, and free cholesterol is known to be toxic to many tissues,” says Henry J. Pownall, PhD, professor of biochemistry in medicine at Houston Methodist Research Institute and corresponding author of the study. “So, any kind of dysfunction in HDL can also be a risk factor for many diseases.”

To study HDL dysfunction, the researchers worked with preclinical mouse models that had abnormally high levels of HDL cholesterol in their bloodstream. While this made them ideal for studying atherosclerosis, Rosales noticed that these mice were also completely sterile.

“Cholesterol is the backbone of all steroidal hormones, and an orchestra of hormones is needed for a fertile animal,” Rosales said. “We know that the ovaries are studded with receptors for HDL, so the metabolism of HDL has got to play a very important role in fertility for that reason.”

As predicted, when the researchers fed the lipid-lowering drug to sterile rats, both LDL and HDL cholesterol levels decreased, and the animals were temporarily protected from infertility. Inspired by these results, they turned to the bacterial protein serum opacity factor, which is known to be highly selective for HDL.

“Serum opacity factor is known primarily in the context of bacterial strep infection where it acts as a virulence factor. But it also turned out that this protein only reacts to HDL and not to LDL or other lipoproteins.” Rosales said. “We hypothesized that perhaps giving serum opacity factor to these mice might help restore their fertility as well.”

For their next set of experiments, the team engineered an adeno-associated virus to deliver the gene for a serum opacity factor to mice lacking HDL receptors with high blood cholesterol. When the gene was expressed and the bacterial protein was produced, the animals’ HDL cholesterol decreased significantly and their fertility was restored.

Based on these promising preclinical results, the researchers next plan to conduct clinical studies to examine lipid levels in women undergoing treatment for idiopathic infertility, where the underlying cause is not fully known. If these patients have high HDL levels, the researchers say that serum opacity factor could be a future line of treatment.

Rosales said, “Even if we help 1 percent of women who are struggling to conceive, it would be life-changing for them, and I think we can make the most impact with our research.” Can.”

The text of this story is published from a wire agency feed without any modification. Only the headline has been changed.


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